Journal article
The role of environmentally mediated drug resistance in facilitating the spatial distribution of residual disease
- Abstract:
- The development of de novo resistance is a major disadvantage in molecularly targeted therapies. While much focus is on cell-intrinsic mechanisms, the microenvironment is also known to play a crucial role. This study examines interactions between cancer cells and cancer associated fibroblasts (CAFs) to understand the local crosstalk facilitating residual disease. Using a hybrid-discrete-continuum model, we explore how treatment-induced stress responses can elicit CAF activation and how breaks in treatment allow microenvironment normalisation. We investigate how fluctuating environmental conditions shape the local crosstalk and ultimately drive residual disease. Our experimentally calibrated model identifies environmental and treatment conditions that allow tumour eradication and those that enable survival. We find two distinct mechanisms that underpin residual disease: vasculature-limited drug delivery and CAF-mediated rescue. This work provides a better understanding of the mechanisms that drive the creation of localised residual disease, crucial to informing the development of more effective treatment protocols.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Supplementary materials, pdf, 2.9MB, Terms of use)
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(Preview, Version of record, pdf, 3.2MB, Terms of use)
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- Publisher copy:
- 10.1038/s42003-025-08585-9
Authors
+ Engineering and Physical Sciences Research Council
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- Funder identifier:
- https://ror.org/0439y7842
- Grant:
- EP/W523963/1
- Publisher:
- Springer Nature
- Journal:
- Communications Biology More from this journal
- Volume:
- 8
- Issue:
- 1
- Article number:
- 1189
- Publication date:
- 2025-08-09
- Acceptance date:
- 2025-07-24
- DOI:
- EISSN:
-
2399-3642
- Language:
-
English
- Pubs id:
-
2250764
- Local pid:
-
pubs:2250764
- Deposit date:
-
2025-07-26
- ARK identifier:
Terms of use
- Copyright holder:
- Milne et al.
- Copyright date:
- 2025
- Rights statement:
- © The Author(s) 2025. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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